Single-Cell Optogenetic Control of Calcium Signaling with a High-Density Micro-LED Array.

Precise optogenetic control, ideally down to single cells in dense cell populations, is essential in understanding the heterogeneity of cell networks. Devices with such capability, if built in a chip scale, will advance optogenetic studies at cellular levels in a variety of experimental settings. Here we demonstrate optogenetic control of intracellular Ca dynamics at the single cell level using a 16-μm pitched micro-light emitting diode (LED) array that features high brightness, small spot size, fast response, and low voltage operation. Individual LED pixels are able to reliably trigger intracellular Ca transients, confirmed by fluorescence microscopy and control experiments and cross-checked by two genetically coded Ca indicators. Importantly, our array can optogenetically address individual cells that are sub-10 μm apart in densely packed cell populations. These results suggest the possible use of the micro-LED array toward a lab-on-a-chip for single-cell optogenetics, which may allow for pharmaceutical screening and fundamental studies on a variety of cell networks.